Expression of the PDGF-2 gene has been detected in a variety of human cells, both normal and transformed. Never in our survey were we able to detect expression of PDGF-2 in normal cells susceptible to the mitogenic effect of PDGF. As a means of further assessing the meaning of PDGF-2 expression in susceptible cells, molecular constructs containing all of the coding sequences of the normal PDGF-2 gene were prepared and introduced into NIH/3T3 fibroblasts. When provided with a retrovirus LTR promoter, the normal PDGF-2 gene was converted to an oncogene. These findings provide strong evidence for the concept that transcriptional activation of the PDGF-2 gene is involved in the process leading to tumors of connective tissue origin.